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Flad, L.M.* ; Weisser, T.* ; Liedl, J.* ; Gard, F.* ; Petrera, A. ; von Toerne, C. ; Hauck, S.M. ; Deeg, C.A.* ; Kleinwort, K.J.H.*

Inhibitory impact of A1 and A2 cow's milk on human peripheral blood mononuclear cells identifies TOM1 as a candidate anti-inflammatory mediator.

Front. Immunol. 17:1728935 (2026)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Introduction: Cows milk has long been discussed as a modulator of immune response, with a particular focus on different health effects of its beta-casein variants A1 and A2. To date, the factors in milk which may be responsible for effects on the human immune system remain unknown, revealing a lack of information that warrants further investigations. We previously found that both A1 and A2 milk inhibit Concanavalin A-induced human peripheral blood mononuclear cells (PBMC) proliferation. Accordingly, this study aimed to investigate the underlying mechanisms of the inhibitory effect. Methods: In a first step, we narrowed down the size-range of possible causative factors in A1 and A2 milk samples by separating each milk type in a high (> 100 kDa; HWF) and a low molecular weight fraction (< 100 kDa, LWF) and used them in co-incubation with Concanavalin A stimulated human PBMC. In in vitro proliferation assays, we identified HWFs as the inhibitory fractions and analyzed the PBMCs supernatant proteomes using high-resolution LC-MS/MS to assess changes in the cellular response to HWFs. Olink proteomics was used to asses the influence of the candidate protein on Immune-Response-Marker release of PBMC. Results: HWFs of milk exert an inhibitory effect on human PBMC. Among several candidates, Target of Myb protein 1 (TOM1) emerged as the only protein markedly increased in the supernatant proteomes after co-incubation with the HWFs of A1 and A2 milk. Further in vitro proliferation assays revealed an inhibitory impact of TOM1 on stimulated humane PBMC. Olink analysis of PBMC Immune-Response-Marker secretion reinforced a possible role for TOM1 as anti-inflammatory mediator in milk involved in the regulation of immune response via Interleukin-1 beta-associated signaling. Discussion: Our findings provide new insights into milk-induced immune regulation and identify TOM1 as a promising anti-inflammatory factor.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter A1/A2 milk fractions; ConA; immunonutrition; Olink; PBMC; proliferation; supernatant proteome; TOM1; Beta-casein Variants; Bovine-milk; In-vitro; Stimulation; Beta-casomorphin-7; Suppression; Activation; Proteins; Release
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 17, Heft: , Seiten: , Artikelnummer: 1728935 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Förderungen Bayerischer Milchfrderungsfond